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In this issue of Neuron , Li, Zhang, et al. 1 find that the bile acid receptor TGR5 in the lateral hypothalamus influences neuronal dynamics underlying stress-induced depression-like behaviors. Inhibition of these neurons produces antidepressant-like effects through a circuit that includes hippocampal CA3 and dorsolateral septum, revealing a novel potential therapeutic for depression. In this issue of Neuron , Li, Zhang, et al. find that the bile acid receptor TGR5 in the lateral hypothalamus influences neuronal dynamics underlying stress-induced depression-like behaviors. Inhibition of these neurons produces antidepressant-like effects through a circuit that includes hippocampal CA3 and dorsolateral septum, revealing a novel potential therapeutic for depression. [ABSTRACT FROM AUTHOR]

Mood and anxiety disorders are complex heterogeneous syndromes that manifest in dysfunctions across multiple brain regions, cell types, and circuits. Biomarkers using brain-wide activity patterns in humans have proven useful in distinguishing between disorder subtypes and identifying effective treatments. In order to improve biomarker identification, it is crucial to understand the basic circuitry underpinning brain-wide activity patterns. Leveraging a large repertoire of techniques, animal studies have examined roles of specific cell types and circuits in driving maladaptive behavior. Recent advances in multiregion recording techniques, data-driven analysis approaches, and machine-learning-based behavioral analysis tools can further push the boundary of animal studies and bridge the gap with human studies, to assess how brain-wide activity patterns encode and drive emotional behavior. Together, these efforts will allow identifying more precise biomarkers to enhance diagnosis and treatment. Mood and anxiety disorders are complex neural-circuit-based conditions that arise from dysfunctions across multiple cell types, brain regions, and circuits. Recent efforts in identifying circuit-based biomarkers using brain-wide activity patterns have shown promising results in stratifying disorder subtypes and identifying effective treatments for patients with mood and anxiety disorders. Advances in multiregion recording techniques, unbiased data-driven analysis approaches, and machine-learning-based behavioral analysis tools now enable animal studies to effectively reverse translate biomarker-based approaches in human studies to understand how brain-wide activity patterns are altered in disease. The combination of these tools with circuit-based manipulations can help researchers investigate the roles of specific cell types, regions, and circuits in emotional information processing, and how neural circuit dysfunctions manifest in maladaptive behavior. [ABSTRACT FROM AUTHOR]

The dentate gyrus (DG) has distinct roles along its dorso-ventral axis. In the mouse, we recently demonstrated that dorsal DG (dDG) stimulation enhances exploratory behavior (Kheirbek et al., 2013). Dopamine (DA) release in the Nucleus Accumbens (NAcc), which belongs to the reward system, could be a key target of dDG mediating this motivation-related behavior. Here, an optogenetic stimulation of either ventral (vDG) or dDG granule cells was coupled with NAcc DA release monitoring using in vivo microdialysis. Only dDG stimulation enhanced NAcc DA release, indicating differential interconnections between dDG and vDG to the reward system. [ABSTRACT FROM AUTHOR]

ABSTRACT Robust incorporation of new principal cells into pre-existing circuitry in the adult mammalian brain is unique to the hippocampal dentate gyrus (DG). We asked if adult-born granule cells (GCs) might act to regulate processing within the DG by modulating the substantially more abundant mature GCs. Optogenetic stimulation of a cohort of young adult-born GCs (0 to 7 weeks post-mitosis) revealed that these cells activate local GABAergic interneurons to evoke strong inhibitory input to mature GCs. Natural manipulation of neurogenesis by aging-to decrease it-and housing in an enriched environment-to increase it-strongly affected the levels of inhibition. We also demonstrated that elevating activity in adult-born GCs in awake behaving animals reduced the overall number of mature GCs activated by exploration. These data suggest that inhibitory modulation of mature GCs may be an important function of adult-born hippocampal neurons. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Memory traces are believed to be ensembles of cells used to store memories. To visualize memory traces, we created a transgenic line that allows for the comparison between cells activated during encoding and expression of a memory. Mice re-exposed to a fear-inducing context froze more and had a greater percentage of reactivated cells in the dentate gyrus (DG) and CA3 than mice exposed to a novel context. Over time, these differences disappeared, in keeping with the observation that memories become generalized. Optogenetically silencing DG or CA3 cells that were recruited during encoding of a fear-inducing context prevented expression of the corresponding memory. Mice with reduced neurogenesis displayed less contextual memory and less reactivation in CA3 but, surprisingly, normal reactivation in the DG. These studies suggest that distinct memory traces are located in the DG and in CA3 but that the strength of the memory is related to reactivation in CA3. [ABSTRACT FROM AUTHOR]

Summary: The dentate gyrus (DG), in addition to its role in learning and memory, is increasingly implicated in the pathophysiology of anxiety disorders. Here, we show that, dependent on their position along the dorsoventral axis of the hippocampus, DG granule cells (GCs) control specific features of anxiety and contextual learning. Using optogenetic techniques to either elevate or decrease GC activity, we demonstrate that GCs in the dorsal DG control exploratory drive and encoding, not retrieval, of contextual fear memories. In contrast, elevating the activity of GCs in the ventral DG has no effect on contextual learning but powerfully suppresses innate anxiety. These results suggest that strategies aimed at modulating the excitability of the ventral DG may be beneficial for the treatment of anxiety disorders. [ABSTRACT FROM AUTHOR]

Although an influence of adult neurogenesis in mediating some of the effects of antidepressants has received considerable attention in recent years, much less is known about how alterations in this form of plasticity may contribute to psychiatric disorders such as anxiety and depression. One way to begin to address this question is to link the functions of adult-born hippocampal neurons with specific endophenotypes of these disorders. Recent studies have implicated adult-born hippocampal neurons in pattern separation, a process by which similar experiences or events are transformed into discrete, non-overlapping representations. Here we propose that impaired pattern separation underlies the overgeneralization often seen in anxiety disorders, specifically post-traumatic stress disorder and panic disorder, and therefore represents an endophenotype for these disorders. The development of new, pro-neurogenic compounds may therefore have therapeutic potential for patients who display pattern separation deficits. [ABSTRACT FROM AUTHOR]

Adult-generated granule cells (GCs) in the dentate gyrus (DG) exhibit a period of heightened plasticity 4-6 weeks postmitosis. However, the functional contribution of this critical window of plasticity to hippocampal neurogenesis and behavior remains unknown. Here, we show that deletion of NR2B-containing NMDA receptors from adult-born GCs impairs a neurogenesis-dependent form of LTP in the DG and reduces dendritic complexity of adult-born GCs, but does not impact their survival. Mice in which the NR2B-containing NMDA receptor was deleted from adult-born GCs did not differ from controls in baseline anxiety-like behavior or discrimination of very different contexts, but were impaired in discrimination of highly similar contexts. These results indicate that NR2B-dependent plasticity of adult-born GCs is necessary for fine contextual discrimination and is consistent with their proposed role in pattern separation. [ABSTRACT FROM AUTHOR]

Dopamine (DA)-dependent corticostriatal plasticity is thought to underlie incremental procedural learning.Aprimary effector of striatal DA signaling is cAMP, yet its role in corticostriatal plasticity and striatum-dependent learning remains unclear. Here, we show that genetic deletion of a striatum-enriched isoform of adenylyl cyclase, AC5 knock-out (AC5KO), impairs two forms of striatum-dependent learning and corticostriatal synaptic plasticity. AC5KO mice were severely impaired in acquisition of a response strategy in the cross maze, a striatum-dependent task requiring a correct body turn to find a goal arm. In addition, AC5KO mice were impaired in acquisition of a motor skill, as assessed by the accelerated rotarod. Slice electrophysiology revealed a deficit in corticostriatal long-term depression (LTD) after high-frequency stimulation of tissue from AC5KO mice. LTD was rescued by activation of either presynaptic cannabinoid type 1 (CB1 ) receptors or postsynaptic metabotropic glutamate receptors (mGluRs), suggesting a postsynaptic role of AC5-cAMP, upstream of endocannabinoid release. In striatopallidal-projecting medium spiny neurons, DA D2 receptors are negatively coupled to cAMP production, and activation of these receptors is required for endocannabinoid release and corticostriatal LTD. Recordings from striatopallidal neurons indicated that this is mediated by AC5, because coactivation of D2 and mGluRs could induce LTD in wild-type but not in AC5KO neurons. To further examine the role of cAMP in corticostriatal plasticity, we elevated cAMP in striatal neurons of wild-type mice via the recording electrode. Under these conditions, corticostriatal LTD was eliminated. Together, these data suggest an AC5-cAMP- endocannabinoid-CB1 signaling pathway in corticostriatal plasticity and striatum-dependent learning. [ABSTRACT FROM AUTHOR]

In associative learning, animals learn to associate external cues or their own actions with appetitive or aversive outcomes. Although the dopamine (DA) system and the striatum/nucleus accumbens have been implicated in both the pavlovian and instrumental form of associative learning, whether specific neuronal signaling mechanisms underlie one form or the other is unknown. Here, we report that the striatum-enriched isoform of adenylyl cyclase (AC), AC5, is selectively required for appetitive pavlovian learning. Mice with genetic deletion of AC5 (AC5KO) acquired instrumental responding yet were unable to use cues that predicted reward delivery. The specificity of this deficit was confirmed by an inability of AC5KO mice to learn a simple appetitive pavlovian conditioning task. Conversely, AC5KO mice showed intact aversive pavlovian learning, suggesting the deficit was specific for learning about appetitive outcomes. Our results suggest that AC5 is a critical component of DA-dependent strengthening of stimulus-reward contingencies. [ABSTRACT FROM AUTHOR]

Hox genes are critical for establishing the segmental pattern of the vertebrate hindbrain. Changes in their expression can alter neural organization of hindbrain segments and may be a mechanism for brain evolution. To test the hypothesis that neurons induced through changes in Hox gene expression can integrate into functional neural circuits, we examined the roles of ectopic Mauthner cells (M-cells) in the escape response of larval zebrafish. The activity of the paired Mauthner cells in rhombomere 4 (r4) has been shown to be critical for generating a high-performance startle behavior in response to stimulation of the tail (Liu and Fetcho,1999). Previous studies have found that misexpression of particular Hox genes causes ectopic M-cells to be generated in r2 in addition to the r4 cells (Alexandra et al., 1996; McClintock et al., 2001). With calcium imaging, we found that the homeotically transformed neurons respond to startle stimuli. To determine the roles of ectopic and endogenous M-cells in the behavior, we lesioned the r2, r4, or both M-cells with cell-specific laser lesion and examined the effect on startle performance. Lesion of the normal M-cells did not decrease escape performance when the ectopic cells were present. These results indicate that the homeotically transformed Mauthner cells are fully functional in the escape circuit and are functionally redundant with normal M-cells. We suggest that such functional redundancy between neurons may provide a substrate for evolution of neural circuits. [ABSTRACT FROM AUTHOR]

In select areas of the brain, neural stem cells produce new neurons throughout life. An elegant new study in this issue of Cell reveals the origins of a stem cell population that persists into adulthood and uncovers a surprising relationship between neurons born in the mature brain and those generated early in development. [ABSTRACT FROM AUTHOR]

How are fear memories organized? In this issue of Neuron , Vetere et al. (2017) take a network-based approach to demonstrate the importance of highly interconnected hub regions in the consolidation of a fear memory. By doing so, they provide an elegant framework for predicting behavior from functional network properties. [ABSTRACT FROM AUTHOR]

Fifteen years ago, the generation of new neurons in adulthood was documented in the human hippocampus, but lingering questions have remained about the extent of this process. In this issue of Cell, Spalding et al. provide elegant evidence for continued neurogenesis into adulthood at rates that suggest it may play a significant role in human behavior. [ABSTRACT FROM AUTHOR]

The article cites a research study that elaborates the role of the dorsal (septal pole) hippocampus and the ventral (temporal pole) hippocampus. It is said that the hippocampus has a functionally heterogeneous structure along its longitudinal axis. Research indicate that the septal pole is responsible for learning and spatial memory, whereas the temporal pole regulates emotional and motivated behaviors.

The article discusses a study which suggests that activation of L-type calcium channels may be the molecular switch for induction of corticostriatal long-term depression (LTD). The authors show that LTD can be induced with only modest presynaptic activity and modest postsynaptic depolarization if there is strong activation of L-type calcium channels. Results suggest that strong activation of L-type calcium channels can override the requirement for phospholipase C (PLC)-dependent calcium release.

The ventral hippocampus (vHPC) has long been thought of as the "emotional" hippocampus. Over the past several years, the complexity of vHPC has come to light, highlighting the diversity of cell types, inputs, and outputs that coordinate a constellation of positively and negatively motivated behaviors. Here, we review recent work on how vCA1 contributes to a network that associates external stimuli with internal motivational drive states to promote the selection of adaptive behavioral responses. We propose a model of vHPC function that emphasizes its role in the integration and transformation of internal and external cues to guide behavioral selection when faced with multiple potential outcomes. • New research shows that vHPC links salient environmental stimuli to internal motivational states, driving diverse behaviors. • vHPC is anatomically complex and routes- information to diverse downstream targets. • Human data indicates that changes in the functional and anatomical connectivity of anterior HPC correlates with mood/anxiety. [ABSTRACT FROM AUTHOR]

Fear memories guide adaptive behavior in contexts associated with aversive events. The hippocampus forms a neural representation of the context that predicts aversive events. Representations of context incorporate multisensory features of the environment, but must somehow exclude sensory features of the aversive event itself. We investigated this selectivity using cell type-specific imaging and inactivation in hippocampal area CA1 of behaving mice. Aversive stimuli activated CA1 dendrite-targeting interneurons via cholinergic input, leading to inhibition of pyramidal cell distal dendrites receiving aversive sensory excitation from the entorhinal cortex. Inactivating dendrite-targeting interneurons during aversive stimuli increased CA1 pyramidal cell population responses and prevented fear learning. We propose subcortical activation of dendritic inhibition as a mechanism for exclusion of aversive stimuli from hippocampal contextual representations during fear learning. [ABSTRACT FROM AUTHOR]

Objective Dopamine (DA) is critical for motor performance, motor learning, and corticostriatal plasticity. The relationship between motor performance and learning, and the role of DA in the mediation of them, however, remain unclear. Methods To examine this question, we took advantage of PITx3-deficient mice ( aphakia mice), in which DA in the dorsal striatum is reduced by 90%. PITx3-deficient mice do not display obvious motor deficits in their home cage, but are impaired in motor tasks that require new motor skills. We used the accelerating rotarod as a motor learning task. Results We show that the deficiency in motor skill learning in PITx3(−/−) is dramatic and can be rescued with levodopa treatment. In addition, cessation of levodopa treatment after acquisition of the motor skill does not result in an immediate drop in performance. Instead, there is a gradual decline of performance that lasts for a few days, which is not related to levodopa pharmacokinetics. We show that this gradual decline is dependent on the retesting experience. Interpretation This observation resembles the long-duration response to levodopa therapy in its slow buildup of improvement after the initiation of therapy and gradual degradation. We hypothesize that motor learning may play a significant, underappreciated role in the symptomatology of Parkinson disease as well as in the therapeutic effects of levodopa. We suggest that the important, yet enigmatic long-duration response to chronic levodopa treatment is a manifestation of rescued motor learning. ANN NEUROL 2010;67:639-647 [ABSTRACT FROM AUTHOR]

Both the dorsal and ventral striatum have been demonstrated to have a critical role in reinforcement learning and addiction. Dissecting the specific function of these striatal compartments and their associated nigrostriatal and mesoaccumbens dopamine pathways, however, has proved difficult. Previous studies using lesions to isolate the contribution of nigrostriatal and mesoaccumbens dopamine in mediating the locomotor and reinforcing effects of psychostimulant drugs have yielded inconsistent and inconclusive results. Using a naturally occurring mutant mouse line, aphakia, that lacks a nigrostriatal dopamine pathway but retains an intact mesoaccumbens pathway, we show that the locomotor activating effects of cocaine, including locomotor sensitization, are dependent on an intact nigrostriatal dopamine projection. In contrast, cocaine reinforcement, as measured by conditioned place preference and cocaine sensitization of sucrose preference, is intact in these mice. In light of the well-established role of the nucleus accumbens in mediating the effects of psychostimulants, these data suggest that the nigrostriatal pathway can act as a critical effector mechanism for the nucleus accumbens highlighting the importance of intrastriatal connectivity and providing insight into the functional architecture of the striatum.Neuropsychopharmacology (2009) 34, 1149–1161; doi:10.1038/npp.2008.117; published online 13 August 2008 [ABSTRACT FROM AUTHOR]

Pair-bond formation depends vitally on neuromodulatory signaling within the nucleus accumbens, but the neuronal dynamics underlying this behavior remain unclear. Using 1-photon in vivo Ca2+ imaging in monogamous prairie voles, we found that pair bonding does not elicit differences in overall nucleus accumbens Ca2+ activity. Instead, we identified distinct ensembles of neurons in this region that are recruited during approach to either a partner or a novel vole. The partner-approach neuronal ensemble increased in size following bond formation, and differences in the size of approach ensembles for partner and novel voles predict bond strength. In contrast, neurons comprising departure ensembles do not change over time and are not correlated with bond strength, indicating that ensemble plasticity is specific to partner approach. Furthermore, the neurons comprising partner and novel-approach ensembles are nonoverlapping while departure ensembles are more overlapping than chance, which may reflect another key feature of approach ensembles. We posit that the features of the partner-approach ensemble and its expansion upon bond formation potentially make it a key neuronal substrate associated with bond formation and maturation. [ABSTRACT FROM AUTHOR]

In vivo calcium imaging through microendoscopic lenses enables imaging of previously inaccessible neuronal populations deep within the brains of freely moving animals. However, it is computationally challenging to extract single-neuronal activity from microendoscopic data, because of the very large background fluctuations and high spatial overlaps intrinsic to this recording modality. Here, we describe a new constrained matrix factorization approach to accurately separate the background and then demix and denoise the neuronal signals of interest. We compared the proposed method against previous independent components analysis and constrained nonnegative matrix factorization approaches. On both simulated and experimental data recorded from mice, our method substantially improved the quality of extracted cellular signals and detected more well-isolated neural signals, especially in noisy data regimes. These advances can in turn significantly enhance the statistical power of downstream analyses, and ultimately improve scientific conclusions derived from microendoscopic data. [ABSTRACT FROM AUTHOR]

Altered dopamine D2 receptor (D2R) binding in the striatum has been associated with abnormal motivation in neuropsychiatric disorders, including schizophrenia. Here, we tested whether motivational deficits observed in mice with upregulated D2Rs (D2R- OEdev mice) are reversed by decreasing function of the striatopallidal "no-go" pathway. To this end, we expressed the Gαi-couplcd designer receptor hM4D in adult striatopallidal neurons and activated the receptor with clozapine-N-oxide (CNO). Using a head-mounted miniature microscope we confirmed with calcium imaging in awake mice that hM4D activation by CNO inhibits striatopallidal function measured as disinhibited downstream activity in the globus pallidus. Mice were then tested in three operant tasks that address motivated behavior, the progressive ratio task, the progressive hold-down task, and outcome devaluation. Decreasing striatopallidal function in the dorsomedial striatum or nucleus accumbens core enhanced motivation in D2R- OEdev mice and control littermates. This effect was due to increased response initiation but came at the cost of goal- directed efficiency. Moreover, response vigor and the sensitivity to changes in reward value were not altered. Chronic activation of hM4D by administering CNO for 2 weeks in drinking water did not affect motivation due to a tolerance effect. However, the acute effect of CNO on motivation was reinstated after discontinuing chronic treatment for 48 h. Used as a therapeutic approach, striatopallidal inhibition should consider the risk of impairing goal-directed efficiency and behavioral desensitization. [ABSTRACT FROM AUTHOR]

Summary Adult-born granule cells (abGCs) have been implicated in cognition and mood; however, it remains unknown how these cells behave in vivo. Here, we have used two-photon calcium imaging to monitor the activity of young abGCs in awake behaving mice. We find that young adult-born neurons fire at a higher rate in vivo but paradoxically exhibit less spatial tuning than their mature counterparts. When presented with different contexts, mature granule cells underwent robust remapping of their spatial representations, and the few spatially tuned adult-born cells remapped to a similar degree. We next used optogenetic silencing to confirm the direct involvement of abGCs in context encoding and discrimination, consistent with their proposed role in pattern separation. These results provide the first in vivo characterization of abGCs and reveal their participation in the encoding of novel information. [ABSTRACT FROM AUTHOR]

Summary Degeneration of dopamine (DA) neurons in Parkinson’s disease (PD) causes hypokinesia, but DA replacement therapy can elicit exaggerated voluntary and involuntary behaviors that have been attributed to enhanced DA receptor sensitivity in striatal projection neurons. Here we reveal that in hemiparkinsonian mice, striatal D1 receptor-expressing medium spiny neurons (MSNs) directly projecting to the substantia nigra reticulata (SNr) lose tonic presynaptic inhibition by GABA B receptors. The absence of presynaptic GABA B response potentiates evoked GABA release from MSN efferents to the SNr and drives motor sensitization. This alternative mechanism of sensitization suggests a synaptic target for PD pharmacotherapy. [ABSTRACT FROM AUTHOR]

Although cortico-striato-thalamo-cortical (CSTC) circuit dysregulation is correlated with obsessive compulsive disorder (OCD), causation cannot be tested in humans. We used optogenetics in mice to simulate CSTC hyperactivation observed in OCD patients. Whereas acute orbitofrontal cortex (OFC)-ventromedial striatum (VMS) stimulation did not produce repetitive behaviors, repeated hyperactivation over multiple days generated a progressive increase in grooming, a mouse behavior related to OCD. Increased grooming persisted for 2 weeks after stimulation cessation. The grooming increase was temporally coupled with a progressive increase in light-evoked firing of postsynaptic VMS cells. Both increased grooming and evoked firing were reversed by chronic fluoxetine, a first-line OCD treatment. Brief but repeated episodes of abnormal circuit activity may thus set the stage for the development of persistent psychopathology. [ABSTRACT FROM AUTHOR]

Adult hippocampal neurogenesis is a unique form of neural circuit plasticity that results in the generation of new neurons in the dentate gyrus throughout life. Neurons that arise in adults (adult-born neurons) show heightened synaptic plasticity during their maturation and can account for up to ten per cent of the entire granule cell population. Moreover, levels of adult hippocampal neurogenesis are increased by interventions that are associated with beneficial effects on cognition and mood, such as learning, environmental enrichment, exercise and chronic treatment with antidepressants. Together, these properties of adult neurogenesis indicate that this process could be harnessed to improve hippocampal functions. However, despite a substantial number of studies demonstrating that adult-born neurons are necessary for mediating specific cognitive functions, as well as some of the behavioural effects of antidepressants, it is unknown whether an increase in adult hippocampal neurogenesis is sufficient to improve cognition and mood. Here we show that inducible genetic expansion of the population of adult-born neurons through enhancing their survival improves performance in a specific cognitive task in which two similar contexts need to be distinguished. Mice with increased adult hippocampal neurogenesis show normal object recognition, spatial learning, contextual fear conditioning and extinction learning but are more efficient in differentiating between overlapping contextual representations, which is indicative of enhanced pattern separation. Furthermore, stimulation of adult hippocampal neurogenesis, when combined with an intervention such as voluntary exercise, produces a robust increase in exploratory behaviour. However, increasing adult hippocampal neurogenesis alone does not produce a behavioural response like that induced by anxiolytic agents or antidepressants. Together, our findings suggest that strategies that are designed to increase adult hippocampal neurogenesis specifically, by targeting the cell death of adult-born neurons or by other mechanisms, may have therapeutic potential for reversing impairments in pattern separation and dentate gyrus dysfunction such as those seen during normal ageing. [ABSTRACT FROM AUTHOR]

Neurons are often considered specialized functional units that encode a single variable. However, many neurons are observed to respond to a mix of disparate sensory, cognitive, and behavioral variables. For such representations, information is distributed across multiple neurons. Here we find this distributed code in the dentate gyrus and CA1 subregions of the hippocampus. Using calcium imaging in freely moving mice, we decoded an animal's position, direction of motion, and speed from the activity of hundreds of cells. The response properties of individual neurons were only partially predictive of their importance for encoding position. Non-place cells encoded position and contributed to position encoding when combined with other cells. Indeed, disrupting the correlations between neural activities decreased decoding performance, mostly in CA1. Our analysis indicates that population methods rather than classical analyses based on single-cell response properties may more accurately characterize the neural code in the hippocampus. • Position, direction of motion, and speed are encoded in CA1 and DG neurons • Single-cell tuning only weakly predicts a cell's importance for position encoding • Non-place cells contribute to position encoding • Disrupting correlations between neurons leads to decreased decoding accuracy in CA1 Using high-resolution calcium imaging and machine learning techniques, Stefanini et al. studied how information about position, direction of motion, and speed is represented in the hippocampus. They show that neurons cooperate to encode this information, and that cells with easily interpretable responses are not necessarily the most important ones. [ABSTRACT FROM AUTHOR]

Animals must discern important stimuli and place them onto their cognitive map of their environment. The neocortex conveys general representations of sensory events to the hippocampus, and the hippocampus is thought to classify and sharpen the distinctions between these events. We recorded populations of dentate gyrus granule cells (DG GCs) and lateral entorhinal cortex (LEC) neurons across days to understand how sensory representations are modified by experience. We found representations of odors in DG GCs that required synaptic input from the LEC. Odor classification accuracy in DG GCs correlated with future behavioral discrimination. In associative learning, DG GCs, more so than LEC neurons, changed their responses to odor stimuli, increasing the distance in neural representations between stimuli, responding more to the conditioned and less to the unconditioned odorant. Thus, with learning, DG GCs amplify the decodability of cortical representations of important stimuli, which may facilitate information storage to guide behavior. • Odor identities are represented in the population activity of DG GCs • Synaptic input from LEC is required for odor coding in DG GCs • Odor classification accuracy in DG is correlated with behavioral discrimination • Learning modifies odor representations in DG GCs Animals use cues in their environments to guide behavior and, with experience, modify internal representations of these cues to guide future behavior. Woods, Stefanini, et al. use high-resolution calcium imaging to show that dentate gyrus granule cells encode and discriminate olfactory information and these representations are enhanced by associative learning. [ABSTRACT FROM AUTHOR]

Summary The hippocampus is traditionally thought to transmit contextual information to limbic structures where it acquires valence. Using freely moving calcium imaging and optogenetics, we show that while the dorsal CA1 subregion of the hippocampus is enriched in place cells, ventral CA1 (vCA1) is enriched in anxiety cells that are activated by anxiogenic environments and required for avoidance behavior. Imaging cells defined by their projection target revealed that anxiety cells were enriched in the vCA1 population projecting to the lateral hypothalamic area (LHA) but not to the basal amygdala (BA). Consistent with this selectivity, optogenetic activation of vCA1 terminals in LHA but not BA increased anxiety and avoidance, while activation of terminals in BA but not LHA impaired contextual fear memory. Thus, the hippocampus encodes not only neutral but also valence-related contextual information, and the vCA1-LHA pathway is a direct route by which the hippocampus can rapidly influence innate anxiety behavior. [ABSTRACT FROM AUTHOR]